Molecular Pharmacology, Vol 14, 347-356, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Changes in Brain Metabolites Induced by Convulsants or Electroshock: Effects of Anticonvulsant Agents

¹ Laboratory of Neurochemistry and Epilepsy Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20014

In general, cyclic 3',5'-GMP concentrations in the cerebellum are elevated by convulsants and diminished by anticonvulsant agents, whereas the levels of cyclic 3',5'-AMP remain unchanged by either treatment. Furthermore, the effect of convulsants on cerebellar cyclic GMP is antagonized by anticonvulsants, and the anticonvulsant activity persists concurrently with the biochemical changes. Maximal electroshock (MES) causes an elevation of cerebellar cyclic AMP during the excitable phase. It is suggested that the elevation of cyclic AMP is inhibitory to the Punkinje cell output and thus favors the seizure state. Phenytoin suppresses the increase in cerebellar cyclic AMP, which would reduce seizure activity. Phenytoin also prevents other metabolic changes induced by MES in the cerebellum, but not the cerebral cortex, indicating that these effects are not simply prevention of anoxia. It is proposed that phenytoin has a locus of action that attenuates the electroshock signal to the cerebellum or suppresses the response by a direct effect on the metabolic machinery.